Fig. 1
From: Coordinate regulation of mutant NPC1 degradation by selective ER autophagy and MARCH6-dependent ERAD
I1061T NPC1 accumulates after lysosomal or proteasomal inhibition. a Primary human fibroblasts homozygous for WT NPC1 (CTRL) or I1061T NPC1 (I1061T) were treated with vehicle (Veh),100 nM bafilomycin A1 (Baf), 10 µM MG132 (MG), or 100 nM epoxomicin (Epox) for 24 h. Quantified at right. b NPC1 protein levels quantified in a were normalized to calculate relative contribution of each pathway to NPC1 degradation. c Time course of NPC1 accumulation after treatment with Baf. Quantified at right. d Patient fibroblasts with the indicated NPC1 mutations were treated for 24 h with vehicle, 100 nM Baf, or 10 µM MG. Normalized relative to CTRL and quantified below. a–d Data are mean ± s.e.m. from three independent experiments. n.s., not significant, *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001 by ANOVA with a–d Tukey’s or c Bonferroni posthoc test (a F = 58.71; c F = 7.68; d F = (c.1947+5G>C/I1061T) 14.91, (P1007A/T1036M) 13.46)
